GSK3B, also known as glycogen synthase kinase 3 beta, is a critical serine/threonine kinase. It serves as a key repressor of the Wnt/β -catenin signaling pathway [3]. GSK3B is involved in multiple biological processes, including autophagy, cell proliferation, migration, and metabolism, and is associated with various diseases such as cancer, osteoarthritis, and Alzheimer's disease [1,2,3,4,8,9]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In cancer research, in colorectal cancer, GSK3B phosphorylates TRAF6 at Thr266, leading to TRAF6 degradation and attenuation of its inhibitory effect on autophagy-dependent CTNNB1 signaling, promoting metastasis [1]. In cervical cancer, silencing GSK3B reduces cell viability, proliferation, and migration both in vitro and in vivo, and it modulates the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition [8]. In lung adenocarcinoma, circ-GSK3B up-regulates GSK3B, suppressing tumorigenesis [3]. In breast cancer, miR-132-3p downregulates GSK3B, enhancing etoposide-induced apoptosis [6]. In allergic rhinitis, miR-214-3p targets GSK3B to facilitate M2 macrophage polarization [7].

In posttraumatic osteoarthritis, overexpression of GSK3B in mice alleviates cartilage degradation by promoting DNMT1-mediated hypermethylation of the NR4A3 promoter [4]. In Alzheimer's disease, conditional overexpression of GSK3β in forebrain neurons of mice recapitulates aspects of AD neuropathology such as tau hyperphosphorylation, apoptotic neuronal death, and spatial learning deficit [9]. In glucose and lipid metabolism, inhibition of GSK3B phosphorylation improves glucose and lipid metabolism disorder [5].

In conclusion, GSK3B is a multifunctional kinase involved in numerous biological processes and disease conditions. Model-based research, especially KO/CKO mouse models, has significantly contributed to understanding its role in cancer, osteoarthritis, Alzheimer's disease, and metabolism-related diseases, providing potential therapeutic targets for these diseases.